The chemically induced transformation of liver cells to the neoplastic state is accompanied by changes in the cell phenotype. These changes presumably result from modifications in normal control processes by carcinogens. A large body of evidence has accumulated which demonstrates the importance of messenger RNA (m-RNA) in regulating the phenotypic expression of cells. The exact effect of carcinogens on the metabolism of m-RNA is not known. The object of this proposal is to analyze polysomal m-RNAs from normal tissue and hepatocellular carcinomas to determine if differences exist between these RNAs. Polysomal m-RNA will be isolated by affinity chromatography on poly (U) Sepharose and hybridized to labeled single copy DNA. RNA-driven saturation experiments will be performed to compare RNA extracted from liver and hepatocellular carcinomas. To make a more precise analysis possible procedures will be developed to purify alpha-fetoprotein m-RNA, a protein produced in large amounts by many hepatocellular carcinomas but not by normal tissue. This messenger will be isolated by a combination of cell fractionation, antibody precipitation, and affinity chromatography. Once alpha-fetoprotein m-RNA has been purified, it will be used to synthesize a complementary DNA c-DNA probe. This probe can then be used to analyze the modifications in alpha-fetoprotein m-RNA induced by exposure to carcinogens.